Cigarette smoking continues to have a major impact on morbidity and mortality, despite attempts to educate smokers and to improve smoking cessation interventions. Persons with schizophrenia are at greater risk for deleterious effects than the general population, due to the large percentage of persons with schizophrenia (60%-70%) who smoke cigarettes. This subset of the population are more likely to be heavier smokers, are three times more likely to start and five times less likely to quit smoking than people in the general population. Craving is a significant barrier to cessation, and may be experienced differently by persons with schizophrenia compared to the general population. This K23 mentored-research patient oriented career development award, submitted by Principal Investigator Dr. Heidi Wehring, focuses on craving and testing a novel craving intervention for smokers with schizophrenia. This focus fits well within the NIDA 5-Year Strategic Plan regarding substance abuse and treatment in persons with co-occurring mental disorders, and is consistent with the NIH mission to foster discoveries, innovative research strategies, and their applications by supporting research in the understanding of mental, addictive, and physical disorders. Dr. Wehring has a long-term career goal of becoming an independent investigator of treatment research for persons with schizophrenia who are dually diagnosed with a substance use disorder, specifically to determine novel approaches to the challenge of nicotine cessation. This may be done through using research to better define craving, abstinence, and other factors that may be targeted by pharmacological or nonpharmacological interventions. This K23 proposal has both research and training aims and goals. Short-term goals include contributions to the field of craving research in schizophrenia and Dr. Wehring's development as an independent investigator. These goals will be accomplished by a research proposal aiming to further define components of tobacco craving in smokers with schizophrenia, to determine the effects of minocycline on cigarette craving and smoking intensity via a pilot study, and to determine the relationship between changes in craving, smoking intensity, and responses to individualized cues/triggers to craving in smokers with schizophrenia. Dr. Wehring will be mentored by Dr. Deanna Kelly, an expert in schizophrenia, clinical trials, and dual diagnosis, and Dr. Stephen Heishman, an expert in tobacco, nicotine pharmacology, and cue-elicited craving, and will benefit from the support of Consultants Dr. Robert McMahon, an expert in biostatistics and research design and A. Eden Evins, with expertise in nicotine use in schizophrenia. Dr. Wehring will also pursue coursework during the K award period to increase skills and develop expertise necessary to become an independent investigator. This project will provide pilot data to build future research focusing on the development of interventions for smoking cessation in persons with schizophrenia. This is of paramount importance, as the understanding of underlying aspects of substance use will be instrumental in creation of effective interventions.